Let us now talk about a fascinating disease Leishmaniasis. Let's review its pathophysiology, clinical manifestations, and treatment. Leishmania multiplies in cells of the mononuclear phagocyte system. Such as monocytes, macrophages, histiocytes, Kupffer cells, and reticuloendothelial cells in the liver and spleen. Following a sandfly bite, the skin is inoculated with promastigotes. They are phagocytized, mature into amastigotes, and multiply intracellularly. At this point the infection may be eradicated in some hosts, and they may become immune to reinfection with this Leishmania species. In other patients, the infection disseminates hematogenously to multiple organs in a process known as visceral Leishmaniasis. A local cutaneous infection may occur at the inoculation site. Vigorous local inflammatory responses may follow. In some persons the lesion heals spontaneously. In others, a chronic localized infection develops which is disfiguring. In others, the infection spreads to adjacent mucosal surfaces. Post-Kala Azar dermal Leishmaniasis or diffuse cutaneous Leishmaniasis may occur. In some hosts dissemination occurs throughout the mononuclear phagocyte system in multiple organs including the spleen, liver, bone marrow and lymphoid tissue. These organs may demonstrate organisms within macrophages and granulomatous inflammation. Chronic diseases which cause immune compromise may predispose to dissemination such as HIV infection and malnutrition. Cutaneous lesions have an incubation period of 1 week to 2 months. Typically they begin as an ulceration, and may resolve spontaneously or progressively worsen. Here we see a Leishmanian skin ulcer. Note the clean ulceration base, the raised edge and the surrounding erythema. For visceral Leishmania, the incubation period may be 3 weeks to 2 years, although it's usually 2 to 4 months. Symptoms may include fever, malaise, fatigue, headache, abdominal pain, anorexia and diarrhea. Acutely skin lesions may appear as an ulcer and drain. They may occur anywhere but are most commonly seen on limbs. Chronic skin lesions due to leishmania may have very diverse appearances. Clinical suspicion and biopsy are essential to establish the diagnosis. In visceral Leishmaniasis, spenomegaly is nearly universal and may be massive. Hepatomegaly is also common. Severe disease may include emaciation and marked abdominal distention. Severe disease may be further complicated by intercurrent infections such as pneumonia, sepsis, TB, brucellosis and dysentery. In visceral Leishmaniasis there my be hypergammaglobulinemia and hypoalbuminemia. Liver enzymes are commonly elevated. Pancytopenia is very common. Diagnosis is made by demonstration of the organism, which can commonly be done through splenic puncture, liver or bone marrow biopsy, lymph node aspiration, or staining of peripheral blood buffy coat. In terms of treatment, skin lesions may heal spontaneously and may not need treatment. Individualized treatment decisions are needed depending on the host risk of dissemination, severity of the skin lesion and risk of permanent disfigurement due to scarring. Options for treatment of skin lesions include topical therapy or systemic therapy. Visceral Leishmaniasis requires systemic treatment. Choices for systemic treatment should consider the infecting species of Leishmania, availability of medications, and the severity of disease. The most commonly utilized medication is the pentavalent antimonial compound stibogluconate. Alternative options can include liposomal amphotericin B, pentamidine, anoles and miltefosene. Now let's consider a Case History. A 14 year old boy presented with wasting and abdominal distention. On exam he had a massive hepatosplenomegaly. CBC showed pancytopenia, a splenic puncture was performed and revealed Leishmania organisms. Treatment was initiated with stibogluconate and he recovered well.
